BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity...Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.展开更多
BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In thi...BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.展开更多
Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non...Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.展开更多
Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major dif...Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer(NSCLC). To date, surgical resection is the primary mode of treatment for stage?Ⅰ?and Ⅱ NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.展开更多
A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most...A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.展开更多
Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resista...Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.展开更多
Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Da...Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.展开更多
Objective: To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after first-line chemotherapy in Ch...Objective: To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after first-line chemotherapy in Chinese population. Methods: Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time (OS), the second end point was disease control rate (DCR) and progression-free survival time (PFS). DCR included complete response (CR) plus partial response (PR) and plus stable disease (SD). The impact of epidermal growth factor receptor (EGFR) mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography (DHPLC). Results: Among 75 enrolled patients, the overall response rate was 37% and the DCR (CR + PR +SD) was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type (25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively). In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS (P=0.029 and 0.017, respectively), however, rash status was the predictor in terms of PFS (P=0.027). Conclusion: Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has ev...Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.展开更多
AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lu...AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.展开更多
Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic datab...Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.展开更多
AIM:To study the effects of mesenchymal stem cell(MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation.METHODS: In our transplantation center, 6 isolated in...AIM:To study the effects of mesenchymal stem cell(MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation.METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis(n = 4), Crohn's disease(n = 1) and intestinal aganglionosis(n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient's bone marrow was passedinto the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant.RESULTS: The median follow-up for these patients was 10.6 mo(min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to antirejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2nd and 3rd months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13th, 25th and 30th month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation.CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.展开更多
Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemot...Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.展开更多
Objective: To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy (3D-CRT) for locally advanced non-small cell lung cancer (NSCLC) . Methods: From April 2002 to Jun...Objective: To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy (3D-CRT) for locally advanced non-small cell lung cancer (NSCLC) . Methods: From April 2002 to June 2005, 38 pa-tients with inoperable stage III NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m2 on days 1, 8, 15, 22, 29, 36. 3D-CRT was delivered up to a total dose of 60–64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results: The overall response rates of primary tumor and mediastinum metastatic node were 86.8% (33/38) and 90.6% (29/32) respectively, and 91.7% (22/24) and 78.6% (11/14) for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis (RTOG I/II), however, all of them were cured. Conclusion: Con-current application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.展开更多
Small cell lung cancer [SCLC] is a devastating form of cancer, with most patients harbouring extensive disease at diagnosis and survival of less than 5% at five years. Progress in novel therapies has been limited. Thi...Small cell lung cancer [SCLC] is a devastating form of cancer, with most patients harbouring extensive disease at diagnosis and survival of less than 5% at five years. Progress in novel therapies has been limited. This specialist review explores current targeted therapy options and potential areas of development.展开更多
Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure.Based on the underlying cel...Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure.Based on the underlying cellular and molecular mechanisms of a liver fibrosis,there has been proposed several kinds of approaches for the treatment of liver fibrosis.Recently,liver gene therapy has been developed as an alternative way to liver transplantation,which is the only effective therapy for chronic liver diseases.The activation of hepatic stellate cells,a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis.Several targeted strategies have been developed,such as antisense oligodeoxynucleotides,RNA interference and decoy oligodeoxynucleotides to overcome this barriers.With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis,and particularly,of the targeted gene therapy using short RNA and DNA segments.展开更多
Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease prog...Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). Results: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR], 0.99; 95% Confidence Interval [CI]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% CI: 0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% CI: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. Conclusions: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.展开更多
Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer(NSCLC) without disease progress...Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer(NSCLC) without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region(China) from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy(treatment group, n = 32) and best supportive care(control group, n = 32). Disease control and progression-free survival(PFS) were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different(χ2 = 26.532, P = 0.001). The median PFS for the treatment group and control group was 6.0 months [95% confidence interval(CI) = 4.3–7.9 months] and 3.2 months(95% CI = 2.6–3.8 months), respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.展开更多
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81974500,81773678)the CAMS Innovation Fund for Medical Sciences(Grant No.:2022-I2M-2-001).
文摘Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
文摘BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.
文摘Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.
文摘Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer(NSCLC). To date, surgical resection is the primary mode of treatment for stage?Ⅰ?and Ⅱ NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.
文摘A desmoplastic small round cell tumor (DSRCT) is a rare, aggressive mesenchymal neoplasm. Although a DSRCT can develop at various sites, the intraabdominal site is the most common location. These tumors are found most commonly among young adolescents and the prognosis is extremely poor. Multimodal treatment with surgery, chemotherapy and radiotherapy is very important for these rare cases, and this treatment can improve patient survival. In this report, we describe the case of an 8-year-old boy diagnosed with DSRCT located in the retroperitoneal space. The patient has undergone surgical resection and adjuvant chemoradiation therapy, and is currently alive without disease recurrence.
文摘Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.
文摘Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.
基金supported by the grants from the National "863" High Technology Research and Development Program of China (No.2006AA02A401)the Capital Development Foundation of Beijing (No.30772472)
文摘Objective: To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients who obtained disease control (DC) after first-line chemotherapy in Chinese population. Methods: Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time (OS), the second end point was disease control rate (DCR) and progression-free survival time (PFS). DCR included complete response (CR) plus partial response (PR) and plus stable disease (SD). The impact of epidermal growth factor receptor (EGFR) mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography (DHPLC). Results: Among 75 enrolled patients, the overall response rate was 37% and the DCR (CR + PR +SD) was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type (25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively). In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS (P=0.029 and 0.017, respectively), however, rash status was the predictor in terms of PFS (P=0.027). Conclusion: Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
基金supported by the Intramural Research Program National Institute on Aginq,NIH。
文摘Toxic aggregated amyloid-βaccumulation is a key pathogenic event in Alzheimer’s disease.Treatment approaches have focused on the suppression,deferral,or dispersion of amyloid-βfibers and plaques.Gene therapy has evolved as a potential therapeutic option for treating Alzheimer’s disease,owing to its rapid advancement over the recent decade.Small interfering ribonucleic acid has recently garnered considerable attention in gene therapy owing to its ability to down-regulate genes with high sequence specificity and an almost limitless number of therapeutic targets,including those that were once considered undruggable.However,lackluster cellular uptake and the destabilization of small interfering ribonucleic acid in its biological environment restrict its therapeutic application,necessitating the development of a vector that can safeguard the genetic material from early destruction within the bloodstream while effectively delivering therapeutic genes across the bloodbrain barrier.Nanotechnology has emerged as a possible solution,and several delivery systems utilizing nanoparticles have been shown to bypass key challenges regarding small interfering ribonucleic acid delivery.By reducing the enzymatic breakdown of genetic components,nanomaterials as gene carriers have considerably enhanced the efficiency of gene therapy.Liposomes,polymeric nanoparticles,magnetic nanoparticles,dendrimers,and micelles are examples of nanocarriers that have been designed,and each has its own set of features.Furthermore,recent advances in the specific delivery of neurotrophic compounds via gene therapy have provided promising results in relation to augmenting cognitive abilities.In this paper,we highlight the use of different nanocarriers in targeted gene delivery and small interfering ribonucleic acid-mediated gene silencing as a potential platform for treating Alzheimer’s disease.
基金Supported by Institute for Innovation,Science and Technology Flanders(IWT),NO:121114
文摘AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.
文摘Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.
文摘AIM:To study the effects of mesenchymal stem cell(MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation.METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis(n = 4), Crohn's disease(n = 1) and intestinal aganglionosis(n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient's bone marrow was passedinto the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant.RESULTS: The median follow-up for these patients was 10.6 mo(min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to antirejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2nd and 3rd months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13th, 25th and 30th month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation.CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.
文摘Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.
文摘Objective: To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy (3D-CRT) for locally advanced non-small cell lung cancer (NSCLC) . Methods: From April 2002 to June 2005, 38 pa-tients with inoperable stage III NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m2 on days 1, 8, 15, 22, 29, 36. 3D-CRT was delivered up to a total dose of 60–64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results: The overall response rates of primary tumor and mediastinum metastatic node were 86.8% (33/38) and 90.6% (29/32) respectively, and 91.7% (22/24) and 78.6% (11/14) for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis (RTOG I/II), however, all of them were cured. Conclusion: Con-current application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.
文摘Small cell lung cancer [SCLC] is a devastating form of cancer, with most patients harbouring extensive disease at diagnosis and survival of less than 5% at five years. Progress in novel therapies has been limited. This specialist review explores current targeted therapy options and potential areas of development.
基金Supported by National Research Foundation of Korea Grant funded by the Korean Government,No.2012R1A1A401015639
文摘Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure.Based on the underlying cellular and molecular mechanisms of a liver fibrosis,there has been proposed several kinds of approaches for the treatment of liver fibrosis.Recently,liver gene therapy has been developed as an alternative way to liver transplantation,which is the only effective therapy for chronic liver diseases.The activation of hepatic stellate cells,a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis.Several targeted strategies have been developed,such as antisense oligodeoxynucleotides,RNA interference and decoy oligodeoxynucleotides to overcome this barriers.With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis,and particularly,of the targeted gene therapy using short RNA and DNA segments.
基金supported by the grants from the China National Funds for Distinguished Young Scientists (No. 81025012)the Capital Development Foundation (No. 30772472)
文摘Objective: To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment (immediate group) vs. those received delayed treatment upon disease progression as second-line therapy (delayed group). Methods: The study included 159 no-small-cell lung cancer (NSCLC) patients who received gefitinib or erlotinib as maintenance treatment in the immediate group (85 patients) or as second-line therapy in the delayed group (74 patients). The primary end point was progression-free survival (PFS). EGFR mutation status was detected using denaturing high-performance liquid chromatography (DHPLC). Results: PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively (hazard ratio [HR], 0.99; 95% Confidence Interval [CI]: 0.69-1.42; P=0.947). In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group (HR, 0.48; 95% CI: 0.27-0.85; P=0.012). In patients with wild type EGFR, the risk for disease progression was comparable between the two groups (HR, 1.23; 95% CI: 0.61-2.51; P=0.564). No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival (OS) (26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI: 0.27 to 1.06; P=0.072). There was also no difference in the incidence of adverse events between the two groups. Conclusions: EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.
文摘Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer(NSCLC) without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region(China) from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy(treatment group, n = 32) and best supportive care(control group, n = 32). Disease control and progression-free survival(PFS) were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different(χ2 = 26.532, P = 0.001). The median PFS for the treatment group and control group was 6.0 months [95% confidence interval(CI) = 4.3–7.9 months] and 3.2 months(95% CI = 2.6–3.8 months), respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.